Thermal analysis encompasses an extremely wide spectrum of activities and a large variety of experimental methods and apparatus. The key thermal property measured is the heat capacity of a sample of known mass, from which the specific heat of the sample, which may be solid or liquid, can be calculated. Moreover, basic thermodynamic functions such as phase transition enthalpies as well as reaction kinetics can also be derived. In addition to measuring heat capacities, other heat effects which accompany chemical changes are also of great interest.
There are many approaches to measuring heats of reaction. These approaches include the classical calorimetric methods as well as various types of flow-through calorimeters methods. The prior art approaches to flow-through measurement of heats of reaction have, however, not been sufficiently stable nor sensitive to small changes in heats of reaction, particularly with regard to measurements involving small reactant concentrations. Moreover, the prior art approaches have been too sensitive to flow changes to permit precise measurements.
To date, most of the research involving calorimetric measurements has been carried out by means of known closed cell-type calorimeters. Flow calorimeters have been known and in use and their advantages over other types of calorimeters when dealing with fluid systems wherein chemical equilibrium is rapidly reached, are well recognized. Some highly sensitive forms of flow calorimeters have been developed and are generally referred to as flow microcalorimeters.
A significant improvement in the field of calorimeters has been the development of differential calorimeters. In general, a differential calorimeter is a sophisticated analytical instrument which measures thermal characteristics of a sample material. Specifically, in a differential calorimeter a sample channel and a reference channel are controllably heated over time and the temperature of each monitored. The thermal characteristics of the reference material are known and, preferably the reference material is chosen to be a material that does not undergo a transformation during analysis. Thus, when the sample material undergoes a transformation such as sublimation, boiling, reaction, or the like, that transformation is clearly discernable when compared to the reference material. By knowing the temperature at which a transformation occurs, as well as the energy either absorbed or expended during the transformation, the sample material can be rather accurately characterized.
Particularly in biological sciences, batch-type, heat-conduction microcalorimeters have been widely used. However, despite extensive refinements, motion artifacts and mixing problems together with reequilibration times between runs have limited the effective sensitivity to approximately 60 .mu.J and throughput to about 3 or 4 runs per day.
The present invention is a significant improvement over the prior art calorimetry methods and apparatus. In particular, the microcalorimeter of the present invention has a sensitivity that is three orders of magnitude greater than that for comparable microcalorimeters and is capable of attaining this sensitivity while using sample amounts which may be two orders of magnitude smaller than those used in other known microcalorimeters.